Increases in masker variability have been shown to increase the effects of informational masking in non-speech listening tasks, but relatively little is known about the influence that masker uncertainty has on the informational components of speech-on-speech masking. In this experiment, listeners were asked to extract information from a target phrase that was presented in their right ear while ignoring masking phrases that were presented in the same ear as the target phrase and in the ear opposite the target phrase. The level of masker uncertainty was varied by holding constant or “freezing” the talkers speaking the masking phrases, the semantic content used in the masking phrases, or both the talkers and the semantic content in the masking phrases within each block of 120 trials. The results showed that freezing the semantic content of the masking phrase in the target ear was the only reduction in masker uncertainty that ever resulted in a significant improvement in performance. Providing feedback after each trial improved performance overall, but did not prevent the listeners from making incorrect responses that matched the content of the frozen target-ear masking phrase. However, removing the target-ear contents corresponding to the masking phrase from the response set resulted in a dramatic improvement in performance. This suggests that the listeners were generally able to understand both of the phrases presented to the target ear, and that their incorrect responses in the task were almost entirely a result of their inability to determine which words were spoken by the target talker.